The overall goals of this project are to determine the structural, perfusion, and chemical changes of the brain that: 1) occur in frontotemporal lobar degeneration (FTLD) and progressive supranuclear palsy (PSP); 2) distinguish FTLD and PSP from Alzheimer's disease (AD); and 3) accompany the cognitive and behavioral symptomatology of FTLD and PSP. These goals will be accomplished by performing structural MRI, spinlabeled perfusion MRI (pMRI), and three dimensional MR Spectroscopic Imaging (3D-MRSI) on a total of 75 patients with FTLD syndromes, 30 patients with PSP, 75 patients with AD, and 50 age-matched, cognitively-normal controls (CN) during the five year period of this project. In addition, 48 subjects with FTLD, 24 with PSP, and 48 with AD will be studied at least once annually, and many subjects will be studied several times annually, to determine the rates of change. This project will test hypotheses in the following categories: 1) comparisons between groups such as comparison of FTLD with controls, comparison of FTLD with AD, comparison of PSP with controls, FTLD, and AD, and comparison between subtypes of FTLD and controls; 2) associations between neuroimaging and cognition in FTLD; and 3) longitudinal declines of volume, CBF, and NAA in FTLD, PSP, and AD. This project will provide new information concerning the brain changes which occur in FTLD. The results of this project will provide detailed information concerning the regions affected by FTLD and differences between FTLD and other dementias. It is expected that new information concerning the anatomical substrate of FTLD symptomatology will be generated. This will lead to improved methods for the differential diagnosis of FTLD. The information for this project will also be useful in identifying objective markers of FTLD which can be used to monitor disease progression, and to assess the effectiveness of medication in future clinical trials.